Trastuzumab Pamirtecan Shows Efficacy in Phase 3 for HER2-Positive Breast Cancer

The phase 3 DYNASTY-Breast01 study (NCT06265428) investigating the novel antibody-drug conjugate (ADC), trastuzumab pamirtecan (BNT323/DB-1303), has met its primary end point of progression-free survival (PFS).¹ The positive topline data from this study represents a significant advancement for this next-generation therapy and its potential role in treating HER2-positive unresectable or metastatic breast cancer.

“This is a milestone in the fruitful collaboration with our colleagues at DualityBio,” said Özlem Türeci, MD, chief medical officer and co-founder at BioNTech, in a press release. “We believe that trastuzumab pamirtecan is an ADC candidate with enormous potential, which makes it an important asset in our global oncology strategy, including combinational approaches. It is the first of our late-stage oncology programs to meet its primary endpoint in a pivotal phase 3 trial and also highlights our commitment to bringing novel oncology treatments with distinct profiles to patients.”

The full data will be shared with regulatory authorities in China in preparation for a biologics license application filing.

Study Design

The phase 3 trial, conducted in China, is a randomized, multicenter study designed to evaluate the efficacy and safety of trastuzumab pamirtecan. The study is enrolling patients with HER2-positive breast cancer who have previously been treated with trastuzumab (Herceptin) and a taxane-based chemotherapy regimen. Patients are randomized to receive trastuzumab pamirtecan or trastuzumab emtansine (T-DM1; Kadcyla).²

Along with the primary end point of PFS, secondary end points include overall survival, objective response rate, pharmacokinetics, adverse events, and patient-reported outcomes.

To be eligible for study enrollment, patients are required to have an ECOG performance status of 0 or 1 and an expected survival time of at least 12 weeks. Those who previously received anti-HER2 ADC therapy, have a history of interstitial lung disease, or have uncontrolled infection are not eligible for participation in the study.

About Trastuzumab Pamirtecan

Trastuzumab pamirtecan is a third-generation topoisomerase-1 inhibitor-based ADC that specifically targets HER2. The drug is composed of a HER2-targeting antibody conjugated to a topoisomerase-1 inhibitor payload. This mechanism of action allows for the selective delivery of a cytotoxic agent to cancer cells expressing the HER2 protein, thereby minimizing systemic toxicity to healthy tissues. The efficacy of this targeted approach is particularly relevant for a clinical audience, as it offers a potential new treatment modality for a patient population that may have exhausted other standard-of-care options.

Beyond DYNASTY-Breast01, trastuzumab pamirtecan is also being investigated in a separate global phase 3 study, DYNASTY-Breast02 (NCT06018337), for patients with HER2-low metastatic breast cancer. This additional trial underscores the potential broad applicability of the drug across different HER2 expression levels, a key area of research interest in modern oncology. The expansion into the HER2-low population reflects the evolving understanding of HER2 as a continuum of expression rather than a binary biomarker, opening new therapeutic avenues for a larger patient cohort.

This article was generated with assistance from Google Gemini. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.

REFERENCES:

1. BioNTech and DualityBio Announce Phase 3 Trial of ADC Candidate BNT323/DB-1303 Met Primary Endpoint of Progression Free Survival in HER2-Positive Metastatic or Unresectable Breast Cancer. News release. BioNTech. September 5, 2025. Accessed September 5, 2025. https://tinyurl.com/4k3dae4y

2. A Study to Compare DB-1303/​BNT323 Versus T-DM1 in Breast Cancer. ClinicalTrials.gov. Updated December 12, 2024. Accessed September 5, 2025. https://clinicaltrials.gov/study/NCT06265428